PubMed Health⌕ Search

Biomedical subjects

T Barry

Publications and source records attributed to T Barry.

At least 19 recordsLinked to original sources

Analgesic use and pain coping among patients with haemophilia.

Pain is an important consequence of bleeding episodes in haemophilia. Previous research has included pain frequency and severity among measures of illness-related disability and quality of life in haemophilia, but little systematic evidence exists about analgesic use and pain coping in haemophilia. This paper reports cross-sectional findings from a national survey of patients with severe haemophilia type A and type B. Respondents provided information about pain frequency, pain coping strategies (using the haemophilia-adapted CSQ), use of analgesics and other drugs, and described any concerns they had about their drug use. Participants registered with comprehensive care haemophilia centres did not differ from the rest of the sample on any of the factors recorded. Over one-third of participants expressed concerns about their drug use, the most frequent of which were about dependence on prescribed analgesics. Pain frequency was the most important predictor of analgesic use, but pain coping, and specifically negative thoughts about pain, was associated with concerns about drug use independently of other factors, including analgesic use and pain frequency. Further research will be needed to evaluate possible interventions to promote more effective pain coping in haemophilia, and to examine the possible effects of pain coping on illness outcomes beyond analgesic use, such as well-being and quality of life.

Adaptation, Psychological↗

Variant Richter's syndrome: a rare case of classical Hodgkin's lymphoma developing in a patient with chronic lymphocytic leukemia treated with fludarabine.

We report a case of a 52-year-old male who developed classical Hodgkin's lymphoma (HL) four years after diagnosis of stage Rai II (Binet B) chronic lymphocytic leukemia (CLL). The patient was treated with fludarabine and cyclophosphamide with partial response. Subsequently, he presented with a 6-month history of weight loss and fatigue, and 6 weeks of fever, a progressively enlarged liver and elevated serum LDH level. An inguinal lymph node biopsy revealed both classical Hodgkin's lymphoma, nodular sclerosing type grade 2 and CLL. A bone marrow biopsy showed no Reed-Steinberg cells and an infiltrate composed of only scattered small lymphocytes consistent with CLL. Immuno-histochemical studies of the lymph node were consistent with both CLL and HL phenotypes. A cytogenic examination of the bone marrow revealed an abnormal karyotype (Y-) in 15% of the cell population. Treatment with MOPP/ABVD was started and fever subsided within 3 days. Our case is one of the very few descriptions of a rare Richter's variant of CLL with progression to HL in a CLL patient treated with fludarabine. Since fludarabine has become standard therapy in CLL such Richter's variant could be the result of therapy, an induced prolonged and severe immunosuppression. Clinicians should be aware of such association, which could become more frequent among CLL patients treated with purine analogs.

Antineoplastic Agents↗

Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes.

The antigenic polymorphism of HIV-1 is a major obstacle in developing an effective vaccine. Accordingly, we screened random peptide libraries (RPLs) displayed on phage with antibodies from HIV-infected individuals and identified an array of HIV-specific epitopes that behave as antigenic mimics of conformational epitopes of gp120 and gp41 proteins. We report that the selected epitopes are shared by a collection of HIV-1 isolates of clades A-F. The phage-borne epitopes are immunogenic in rhesus macaques, where they elicit envelope-specific antibody responses. Upon intravenous challenge with 60 MID50 of pathogenic SHIV-89.6PD, all monkeys became infected; however, in contrast to the naive and mock-immunized monkeys, four of five mimotope-immunized monkeys experienced lower levels of peak viremia, followed by viral set points of undetectable or transient levels of viremia and a mild decline of CD4+ T cells, and were protected from progression to AIDS-like illness. These results provide a new approach to the design of broadly protective HIV-1 vaccines.

AIDS Vaccines↗

Consolidation of passive avoidance learning is associated with transient increases of polysialylated neurons in layer II of the rat medial temporal cortex.

Within the rat medial temporal lobe, transient modulations of neural cell adhesion molecule (NCAM) polysialylation have been observed to follow spatial learning. These have been attributed to neuroplastic events associated with the processing of information destined for long term memory consolidation. To determine if similar events are associated with avoidance learning, we investigated change in polysialylated cell number in the entorhinal, perirhinal, and piriform cortex, following acquisition of a passive avoidance task in the rat. Direct quantification of polysialylated neurons in layer II of these cortical regions revealed a significant increase in polysialylated cell frequency at 12 h following passive avoidance training. Unlike spatial learning, the increased expression of polysialylated neurons persisted for up to 24-48 h following training. In the more dorsal aspect of the perirhinal/entorhinal cortex, this increase was found to be specific to learning, as it was not observed in animals rendered amnesic with scopolamine. By contrast, change in polysialylated cell frequency in the ventral aspect of the medial temporal lobe was only partially reduced by amnesic doses of scopolamine. The persisting activation of NCAM polysialylation in the more dorsal aspects of the perirhinal and entorhinal cortex is suggested to reflect the need for more extensive synaptic alterations, as compared to those required for the consolidation of spatial learning. Moreover, the neuroplastic modulations observed in the more ventral regions of the entorhinal and perirhinal cortex appear to be a unique aspect of avoidance conditioning that reflects the activation of alternative learning strategies associated with motivational and/or contextual parameters of the task.

Animals↗

Molecular cloning and phylogenetic analysis of the small cytoplasmic RNA from Listeria monocytogenes.

A molecular cloning strategy has been designed to isolate the gene that encodes the small cytoplasmic RNA (scRNA) component of bacterial signal recognition particles. Using this strategy a putative Listeria monocytogenes scRNA lambda gt11 recombinant clone was isolated. A previously described complementation assay developed to genetically select functional homologues of 4.5S RNA and scRNA of bacteria confirmed that the lambda gt11 recombinant clone isolated encoded for the scRNA from L. monocytogenes. A secondary structure for this scRNA is proposed and a phylogenetic comparison of the 276 base L. monocytogenes scRNA with previously characterised Gram-positive bacterial scRNAs is also presented.

Base Sequence↗

Spinal cord dose is higher than expected in head and neck radiation.

Myelopathy is a feared consequence of radiation therapy. Risk factors are multifocal; therefore, total dose calculation is crucial. We evaluated the contribution of scatter radiation to obtain an accurate cumulative spinal cord dose. Twenty patients undergoing three field head and neck radiation by Cobalt or 6 MV Linac had a total cord dose calculated from direct and scatter radiation. The cord was removed from the radiation field at tumor doses no higher than 4,400 cGy. Total tumor dose ranged from 5,400-7,400 cGy (mean 6060). All patients achieved the prescribed dose and none were lost to follow up (mean 36 months). It was found that scatter radiation can contribute as much as 20% extra dose to the spinal cord. Mean extra dose was 9% (range 1%-20%). This additional dose ranged from 52-810 cGy (mean 339 cGy). No apparent difference was seen with Cobalt or Linac source. Our conclusion was that significant additional dose is delivered to the spinal cord by scatter radiation and that scatter may contribute more to the development of myelopathy than previously believed.

Cobalt Radioisotopes↗

Neurotoxicity of CSF from HIV-infected humans.

Approximately 15-20% of individuals infected with the human immunodeficiency virus will develop severe neurological disease. This may be due in part to virus-induced release of a number of putative neurotoxins. However, there is little information to predict which individuals will progress to dementia or the precise mechanisms that drive pathogenesis. In an effort to identify early markers of neurological disease progression we used an in vitro bioassay with rat cortical neurons to test for the presence of toxins in CSF from 40 HIV-infected humans with mild, minimal or no neurological disease. A subset of HIV-infected individuals was found to have significant toxic activity in CSF indicating that toxic factors may be circulating prior to the development of dementia. The toxicity was concentration dependent and due to a factor with a molecular mass of less than 30 kDa. Only a small proportion of the cell death appeared to be due to apoptosis. Neuronal toxicity was associated with a gradual accumulation of intracellular calcium in a subset of cortical neurons over a period of 1-2 h and in the absence of a significant acute response. Individuals with both high viral burden and high CSF toxicity were significantly more likely to have neurological symptoms. These initial analyses indicate that toxic factors are present in the CSF of HIV-infected patients that could serve as useful markers of neurological disease progression and provide insights into pathogenic mechanisms in vivo.

Acquired Immunodeficiency Syndrome↗

Crystallization and preliminary X-ray diffraction analysis of aspartate aminotransferase from Saccharomyces cerevisiae.

Diffraction-quality crystals of S. cerevisiae cytoplasmic aspartate aminotransferase have been obtained by the hanging-drop vapor-diffusion method in the presence of pyridoxal phosphate and maleic acid, sodium acetate, ammonium acetate and polyethylene glycol. The crystals have the symmetry of the orthorhombic space groups P212121 or P21212 with unit-cell dimensions a = 130.2, b = 134.6 and c = 98.7 A. Square rod-shaped crystals with dimensions of approximately 0.2 x 0.2 x 0.5 mm diffract to spacings of 2 A. The calculated value of the Matthews coefficient, Vm = 2.4 A3 Da-1, is consistent with four subunits of aspartate aminotransferase per asymmetric unit.

Aspartate Aminotransferases↗

Crystal structure of Saccharomyces cerevisiae cytosolic aspartate aminotransferase.

The crystal structure of Saccharomyces cerevisiae cytoplasmic aspartate aminotransferase (EC 2.6.1.1) has been determined to 2.05 A resolution in the presence of the cofactor pyridoxal-5'-phosphate and the competitive inhibitor maleate. The structure was solved by the method of molecular replacement. The final value of the crystallographic R-factor after refinement was 23.1% with good geometry of the final model. The yeast cytoplasmic enzyme is a homodimer with two identical active sites containing residues from each subunit. It is found in the "closed" conformation with a bound maleate inhibitor in each active site. It shares the same three-dimensional fold and active site residues as the aspartate aminotransferases from Escherichia coli, chicken cytoplasm, and chicken mitochondria, although it shares less than 50% sequence identity with any of them. The availability of four similar enzyme structures from distant regions of the evolutionary tree provides a measure of tolerated changes that can arise during millions of years of evolution.

Animals↗

Radiation and chemotherapy improve outcome in oligodendroglioma.

PURPOSE: Oligodendroglioma is a rare central nervous system tumor which may occur in pure or mixed histology. This scarcity results in difficulty in defining optimal management, mainly due to a lack of outcome analysis. Results are further complicated because the reported series include patients treated before megavoltage radiation or computed tomographic (CT) scan development. This makes extrapolation of outcome difficult to apply to modern-era patients. We report results obtained by current treatment and evaluation. METHODS AND MATERIALS: Outcome of all 38 patients (age 5-70 years) pathologically diagnosed between 1975 and 1993 were reviewed. Pure lesions were seen in 14 cases, of which three were anaplastic. The remainder had mixed tumors, of which six contained anaplastic astrocytic elements. Each patient had undergone maximal debulking surgery, but all remained with residual disease on postoperative CT. RESULTS: For nonanaplastic lesions, no local failure was seen in any patient receiving postoperative radiation (60 Gy) and chemotherapy (vincristine, procarbazine, and carmustine). Follow-up ranged from 28 to 240 months (median 125; N = 6). No postoperative therapy or chemotherapy alone resulted in local failure in all nine patients at risk [time to failure (TTF): 2-40 months; median 25]. Radiation alone in doses of 50 Gy at 2 Gy per day resulted in all six patients failing (TTF: 12-52 months; median 36). Achieving 60 Gy at 2 Gy a day allowed five of eight patients to remain disease free (disease-free survival: 24-160 months; median 66), with three failing at 26, 40, and 60 months. All lesions containing anaplastic elements underwent postoperative radiation therapy (60 Gy) and chemotherapy, with five of nine patients alive and well (median disease-free survival: 48 months; range 28-120). CONCLUSION: The combination of radiation and chemotherapy increases local control of oligodendroglioma whether they contain pure, mixed, or anaplastic histology. Radiation alone may offer good local control as long as 60 Gy is delivered. Chemotherapy alone appears to delay TTF and may be useful for pediatric patients.

Adolescent↗

Spatial learning activates neural cell adhesion molecule polysialylation in a corticohippocampal pathway within the medial temporal lobe.

Transient and time-dependent modulations of neural cell adhesion molecule (NCAM) polysialylation in the dentate gyrus of the rodent hippocampus are a feature of spatial and nonspatial forms of learning. In the hippocampal formation, polysialic acid immunoreactivity was localized to granule-like cells and their mossy fibre axons. We now demonstrate the latter to extend to the CA3 region where apparent recurrent and Schaffer collaterals were labelled. The axons of the CA1 pyramidal cell layer were immunopositive, as was the subiculum that they innervate. Layers I and III of the entorhinal cortex stained intensely for polysialic acid; however, these were not visible in the more lateral aspect of this region and were replaced by a single band of immunopositive neurons that extended to include the perirhinal and piriform cortices. After Morris water maze training, the number of polysialylated neurons within the entorhinal cortex exhibited a two- to threefold increase at the 10-12-h posttraining time with respect to that observed immediately after training. This increase was task specific, as no change was observed in freely swimming animals or those required to locate a visible platform. These results suggest the presence of a corticohippocampal pathway involved in the eventual consolidation of memory.

Age Factors↗

Production of PGE2 by bovine cultured airway smooth muscle cells: regulation by cAMP.

Prostaglandin E2 (PGE2) is thought to be an important inhibitory modulator of inflammatory processes in the airway. Previous studies have shown that it is produced by bovine cultured airway smooth muscle (ASM) cells in large quantities, but its regulation by second messengers has not been studied in this tissue. To determine whether PGE2 production by ASM might be an important action of beta-adrenoceptor agonists in asthma, the regulation of PGE2 production by adenosine 3',5'-cyclic monophosphate (cAMP) was assessed using dibutyryl cAMP (DBcAMP), forskolin, and albuterol. DBcAMP increased PGE2 production over a 24-h time course. Forskolin and albuterol both increased PGE2 production over control cells to similar levels after 24 h. Incubation of albuterol-treated cells with propranolol significantly (70%) reduced the stimulatory effect of albuterol on PGE2 production. Incubation of forskolin-treated cells with Rp-cAMP, a cAMP antagonist, inhibited the PGE2 response evoked by forskolin by 80%. Ro-20-1724, a selective inhibitor of type IV phosphodiesterase, stimulated PGE2 production (P = 0.02). Cycloheximide, a protein-synthesis inhibitor, did not inhibit the response to DBcAMP. The effects of DBcAMP were additive with the effects of bradykinin, a proinflammatory mediator known to increase PGE2 production (P < 0.05). These studies suggest that cAMP may play an important regulatory role in stimulating PGE2 production by ASM. This may be a novel beneficial action of beta-adrenoceptor agonists in asthma.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

The ribosomal intergenic spacer region: a target for the PCR based diagnosis of tuberculosis.

SETTING: DNA Diagnostics, The National Diagnostics Centre and University College Hospital, Galway, Republic of Ireland. OBJECTIVE: To investigate the possibility of developing a DNA probe to distinguish the members of the Mycobacterium tuberculosis complex and develop an assay for the detection of M. tuberculosis in sputum. DESIGN: The ribosomal intergenic spacer regions from the members of the M. tuberculosis complex were sequenced and analysed for the ability of this region to provide sequence diversity for DNA probe development. RESULTS: The 100% sequence homology in this region precluded the development of a probe to distinguish the individual members of the M. tuberculosis complex. However it was possible to develop a DNA probe that could specifically detect only the members of the M. tuberculosis complex. CONCLUSION: A specific DNA probe was developed for the detection of the M. tuberculosis complex and its application to M. tuberculosis detection in sputum was demonstrated.

Base Sequence↗

Cognitive-behavior therapy for late-life insomnia.

Twenty-four older adults with persistent psychophysiological insomnia were randomly assigned to an immediate or a delayed cognitive-behavioral intervention in a waiting-list control group design. Cognitive-behavior therapy consisted of an 8-week group intervention aimed at changing maladaptive sleep habits and altering dysfunctional beliefs and attitudes about sleeplessness. Treatment was effective in reducing sleep latency, wake after sleep onset, and early morning awakening, and in increasing sleep efficiency. The magnitude of changes obtained on polysomnographic measures was smaller but in the same direction as that obtained on daily sleep diaries. Sleep improvements obtained by the immediate-treatment group were replicated with the delayed treatment condition. Therapeutic gains were well maintained at 3- and 12-month follow-ups. Clinical validation of outcome was obtained through collateral ratings from the patients and their significant others. The findings indicate that late-life insomnia can be effectively treated with nonpharmacological interventions.

Aged↗